Factors operating in the evolution of the genomes of enteric bacteria will be studied from three points of view: 1. Evolution of enteric bacterial genomes from a primitive ancestral genome may have entailed two sequential doublings of the ancestral genome. Traces of this event may persist in the contemporary enteric genome in the form of partial homologies between genes that lie approximately 90 degrees or 180 degrees apart on the circular genome. 2. Separation of enteric bacteria into genera during evolution may have entailed the addition or deletion of discrete segments of DNA, mediated by active genetic elements such as insertion sequences, transposons or transducing phages. We plan to study intergeneric heteroduplexes of three specific regions of the enteric genome in order to characterize in physical terms such regions of addition or deletion and to attempt to identify the genetic elements that effected divergence of enteric bacteria into separate genera. 3. Evolutionarily conservative forces must be present to counteract the randomizing tendencies of active genetic elements such as transmissable plasmids, transposons and insertion sequences, ensuring a relatively stable gene arrangement in bacteria over many thousands of generations in spite of pressures to change. We plan to learn more about the evolutionarily conservative force or forces that prevent free and unbridled rearrangements of bacterial genomes.